Dual RNAseq shows the human mucosal immunity protein, MUC13, is a hallmark of Plasmodium exoerythrocytic infection
Zou, Bing Yu
Abdel- Haleem Mohamed, Alyaa
Winzeler, Elizabeth A
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Computational Bioscience Research Center (CBRC)
MetadataShow full item record
AbstractThe exoerythrocytic stage of Plasmodium malaria infection is a critical window for prophylactic intervention. Using a genome-wide dual RNA sequencing of flow-sorted infected and uninfected hepatoma cells we identify the human mucosal immunity gene, Mucin13 (MUC13), as strongly upregulated during Plasmodium exoerythrocytic hepatic-stage infection. We confirm that MUC13 expression is upregulated in hepatoma cell lines and primary hepatocytes. In immunofluorescence assays, host MUC13 protein expression distinguishes infected cells from adjacent uninfected cells and shows similar colocalization with parasite biomarkers such as UIS4 and HSP70. We further show that localization patterns are species independent, distinguishing both P. berghei and P. vivax infected cells, and that MUC13 can be used to identify compounds that inhibit parasite replication in hepatocytes across all Human-infecting Plasmodium species. This data presents a novel interface of host-parasite interactions in Plasmodium, in that a component of host mucosal immunity is reprogrammed to assist the progression of infection.
CitationLaMonte G, Orjuela-Sanchez P, Wang L, Li S, Swann J, et al. (2017) Dual RNAseq shows the human mucosal immunity protein, MUC13, is a hallmark of Plasmodium exoerythrocytic infection. Available: http://dx.doi.org/10.1101/183764.
SponsorsWe thank the members of the Winzeler and Lewis labs for advice and critical reading of the manuscript. In addition, we thank Medicines for Malaria Venture for all of their support of the insectary in Peru. We would also like to thank the UCSD Institute for Genomic Medicine Sequencing Core Facility and the UCSD Human Embryonic Stem Cell Flow Cytometry Core Facility for their technical support. G.L. is supported by an A.P. Giannini Post-Doctoral Fellowship. E.A.W. is supported by grants from the NIH (5R01AI090141 and R01AI103058). N.E.L. and S.L received funding from the NIGMS (R35 GM119850) and the Novo Nordisk Foundation through the Center for Biosustainability at the Technical University of Denmark (NNF10CC1016517). The P. vivax work was supported by grants to J.M.V from the NIH (D43TW007120 and U19AI089681). A.N.C received support from a NIH T32 AI 007036 training grant.
PublisherCold Spring Harbor Laboratory